Efficacy and toxicity of Eudragit-coated chitosan–succinyl-prednisolone conjugate microspheres using rats with 2,4,6-trinitrobenzenesulfonic acid-induced colitis

A targeted delivery system for inflammatory bowel disease (IBD), Eudragit L100 (EuL)-coated chitosan (Ch)–succinyl-prednisolone (SP) conjugate microspheres (Ch–SP-MS/EuL), were designed and examined in vivo for efficacy and toxicity. Their preparation was conducted in the same manner as previously; that is, by synthesis of the conjugate by carbodiimide coupling of Ch and SP, conversion into microspheres (Ch–SP-MS), and coating of Ch–SP-MS with EuL. Experimental colitis was induced by instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the colon in rats. Drugs were administered once or twice a day intragastrically for three consecutive days. Visible colitis severity, colon/body weight ratio and myeloperoxidase activity were measured as inflammatory indices. Toxicity was examined from the decrease in the thymus/body weight ratio. Efficacy was dose-dependent and the greatest in the order Ch–SP-MS/EuL > Ch–SP-MS > prednisolone (PD) alone, and Ch–SP-MS/EuL showed excellent recovery of colitis states. Toxicity was the greatest in the order PD ≫ Ch–SP-MS > Ch–SP-MS/EuL. Ch–SP-MS and Ch–SP-MS/EuL reduced significantly the thymic atrophy caused by PD. It was demonstrated that Ch–SP-MS/EuL enhanced effectiveness of PD and reduced toxic side effects of PD greatly. Also, these results established the prediction by previous in vitro and in vivo studies.